The Center achieves these goals through coordinated efforts of established and new investigators, who are located at public and private institutions in each of the four states of the Region. The Center's governance is inclusive and based on reaching a consensus, yet it also is capable of rapid and flexible responses as priorities change or needs arise. Far-flung participants interact at a distance through frequent telecommunications and periodic face-to-face meetings. The research portfolio is balanced between basic and translational research, and it aims for excellence in areas of research strength and regional relevance rather than more comprehensive but superficial coverage. For basic research the range of agents under study includes toxins, viruses, bacteria, and fungi. And these are studied at the molecular, cellular, organismal, and population levels. Program scientists and their laboratories commit to collaboration and cooperation with public health and other governmental agencies faced with new episodes of bioterrorism or major infectious diseases outbreaks. The PSWRCE's major theme is infections of the western U.S., the Pacific Rim, and Latin America of relevance for biodefense or as emerging diseases. Dengue is increasing in incidence and distribution in both Asia and Latin America, and autochthonous transmission within the continental U.S. is a now realistic concern. Arenaviruses, Nipah virus, and West Nile virus are emerging infections of Asia and/or the Americas. Burkholderia pseudomallei is not only a Category B priority agent but growing in impact as a cause of serious illness in Southeast Asia and Australia. California has long been a center for the diagnosis and prevention of infant botulism. In its sylvatic form plague is primarily a zoonosis of the western US, and there are prospects for urban outbreaks in the metropolises of Asia. Coccidioidomycosis, a newly added Category C infection, is an increasingly common chronic disease with greatest risk for residents of the southwestern U.S. and adjoining regions of Mexico. Tularemia owes its name to a county north of Los Angeles. The Center arose largely through a multi-centric, bottom-up, process, rather than a centralized, topdown one. From the outset we adopted an "open source" approach to priority setting and program development. As stated in our 2004 application, "We decided early in the planning that the goals of an RCE in our region could best be achieved if the application's development was open and evolutionary, rather than hierarchical and highly programmed." We continue to hold this principle of management and strategic planning. Other unifying principles that the consortium continues to operate under are these: (i) Each program has projects at two more institutions and is multidisciplinary to foster communication, sharing, and innovation among the researchers. (2) Where a pathogen's biology is not well-characterized, the major emphasis is on basic research, with the goal of translation of the research findings as soon as justified. Examples are Burkholderia and coccidioidomycosis. (3) Where an agent and its pathogenesis is comparatively better defined, greater emphasis is placed on product development and movement of candidate applications toward pre-clinical studies in experimental animals and then clinical or field testing. Examples are the botulinum neurotoxin and plague. (4) Research findings, reagents, and core facilities are shared within the PSWRCE, within the entire RCE network, and with qualified investigators elsewhere in the region and country. (5) Projects not meeting expectations for research excellence and/or translation are terminated and supplanted by new projects through an open, competitive selection process. (6) The direction and priorities for research projects are determined by the scientific quality of new proposals, the existing research and resource capabilities of the Center, and, in an adaptive way, by current critical questions. (7) Consortium members are committed to the integration of research within and between research programs, to full but efficient and effective use of core facilities, and to expedited translation of the research findings to products. There are seven programs in the PSWRCE: dengue, viral zoonoses, botulinum neurotoxin, Burkholderia, tularemia, coccidioidomycosis, and reservoir-targeted vaccines. The last two programs are new. The coccidioidomycosis program recognizes an emerging disease of importance for the region, and the vaccine program offers a novel and cost-effective approach for prevention of human disease. Each program has projects, ranging from two for tularemia and nine for dengue, for a total of 35. As the proposal that follows demonstrates, the projects within each program are integrate with and complementary to each other. Of the 35 principal investigators of projects, 13 (37%) are new to the PSWRCE. The map on the preceding page shows the twenty institutions of the PSWRCE in the four states that constitute Region IX;three other institutions are located outside the region. The institutions include two private companies, a state health department laboratory, and a national laboratory, in addition to academic institutions and research institutes. There will be one foreign site, Nicaragua, associated with a project, but the PSWRCE also has activities in Laos and Malaysia. There are 5 core facilities;these were selected for their specialized services that would not reproduce what most research universities offer locally. A major training component of the RCE is safety under biocontainment conditions, not only researchers and their staffs but, uniquely, also facilities management personnel and first-responders. We will continue to allocate the maximum permitted funds for developmental projects and career development awards, the likes of which have been the source of some of the greatest advances by the Center to date. There will be five major criteria for evaluating the strengths and shortcomings of the Center: (i) The quality and innovativeness of the science, as assessed by different metrics, including an independent peer review of research papers and intellectual property attributable to RCE funding. (2) The number of new collaborations, new investigators to the field, and new research grants that are generated. (3) The attainment of milestones for translating research findings into products or other applications. (4) The effectiveness and reach of training in biosafety in Region IX. (5) The Center's state of readiness to respond to emergencies.